This competitive renewal grant application aims to bring a novel 3D SPECT imaging technique that has substantial advantage over conventional SPECT to a full clinical implementation and evaluation for improved detection of myocardial defect in myocardial perfusion (MP) SPECT and regional wall motion abnormalities in gated MP SPECT. The novel 3D SPECT imaging technique is based on a unique rotating multi-segment slant- hole (RMSSH) collimator, which has much higher detection efficiency as compared to a conventional parallel- hole collimator with the same resolution (e.g., 3 times for 4-segments). It requires simple data acquisition configuration for artifact-free fully 3D image reconstruction and can provide substantially better image quality compared with conventional SPECT imaging techniques. During the last 2 grant funding periods, we have (1) developed fully 3D analytical and iterative image reconstruction methods for RMSSH SPECT, (2) developed compensation methods to improve the quality and quantitative accuracy of RMSSH SPECT images, (3) evaluated its utility in MP and breast imaging using realistic simulation data, (4) designed and constructed a general purpose 4-segment R4SSH collimator, (5) evaluated its application to MP and breast imaging using physical phantoms, and (6) conducted preliminary clinical evaluation of its application to MP in IRB approved patient studies. In particular, we have obtained strong support from a major medical imaging company, Philips Medical Systems, to implement the novel RMSSH SPECT imaging technique on a state-of-the-art Precedence(R) SPECT/CT system in our nuclear medicine clinic. In this final phase of the project, we propose to focus the project on MP and gated MP SPECT in an accelerated 3-year research program. We will work closely with our clinical investigators and industrial partner to bring the innovative SPECT imaging technique to a full clinical implementation. Specifically, we will concentrate our development on the rotating multi-segment variable slant-hole (RMSVSH) collimator design that provides a larger common-volume-of-view (CVOV) for imaging larger hearts and easier patient positioning. To achieve this goal, we propose (1) to develop fully 3D quantitative image reconstruction methods for RMSVSH SPECT, (2) to design and fabricate RMSVSH collimators that are optimized for MP SPECT imaging, (3) to develop optimum implementation methods and evaluate the performance of RMSVSH MP SPECT using realistic simulated data and task-based image evaluation methods, (4) to evaluate the performance of RMSVSH MP SPECT using experimental phantom studies, and (6) to evaluate the application of RMSSH and RMSVSH SPECT to clinical MP and gated SPECT. Based on the substantial progress and advances we have achieved in the previous 2 rounds, and the convincing results from feasibility studies and preliminary clinical studies, the proposed project has a great potential for success. PUBLIC HEALTH RELEVANCE: We propose to bring a novel three-dimensional SPECT imaging technique that has substantial advantage over conventional SPECT to a full clinical implementation and evaluation for improved detection of myocardial defect in myocardial perfusion (MP) SPECT and regional wall motion abnormalities in gated MP SPECT. The novel 3D SPECT imaging technique is based on a unique rotating multi-segment slant-hole (RMSSH) collimator, which has much higher detection efficiency as compared to a conventional parallel-hole collimator with the same resolution (e.g., 3 times for 4-segments). Based on substantial progress and advances, and convincing results from feasibility study and preliminary clinical study, the project has great potential for success.